Sharma M, Gupta Y K
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi.
Life Sci. 2001 Jan 19;68(9):1021-9. doi: 10.1016/s0024-3205(00)01005-5.
Recent reports suggest the involvement of free radicals in the pathophysiology of Alzheimer's disease [AD]. Streptozotocin [STZ] injection in the brain is known to cause cognitive impairment in rats and is likened to sporadic AD in humans. Though STZ is known to cause impairment in glucose and energy metabolism, it is not known whether this is associated with free radical generation. The present study was designed to investigate if the changes in learning and memory by intracerebroventricular administration of STZ are associated with changes in the markers of oxidative stress. Adult male Wistar rats [330-340 g] were injected with intracerebroventricular STZ [3 mg/kg] bilaterally stereotaxically under ketamine anesthesia [70 mg/kg]. The rats were treated with STZ twice, on day 1 and on day 3. The learning and memory behavior was analyzed using passive avoidance paradigms, elevated plus maze and the closed field activity test while the parameters of oxidative stress assessed were malondialdehyde [MDA] and glutathione. The behavioral tests were performed on day 17, 18 and 19. The rats developed significant deficits in learning, memory and cognitive behavior, indicated by deficits in passive avoidance paradigm and elevated plus maze as compared to sham rats. On day 21, the rats were sacrificed under ether anesthesia and the brains were analyzed for biochemical studies. There was a development of oxidative stress in the brain as indicated by significant elevations in malondialdehyde [MDA] levels and decreased levels of glutathione. The study demonstrates that intracerebroventricular STZ may be appropriate model for investigations of antioxidants as potential treatment in Alzheimer's dementia.
近期报告表明自由基参与了阿尔茨海默病（AD）的病理生理过程。已知向大鼠脑内注射链脲佐菌素（STZ）会导致认知障碍，这类似于人类的散发性AD。虽然已知STZ会导致葡萄糖和能量代谢受损，但尚不清楚这是否与自由基生成有关。本研究旨在调查脑室内注射STZ引起的学习和记忆变化是否与氧化应激标志物的变化有关。成年雄性Wistar大鼠（330 - 340克）在氯胺酮麻醉（70毫克/千克）下双侧立体定向脑室内注射STZ（3毫克/千克）。大鼠在第1天和第3天接受两次STZ治疗。使用被动回避范式、高架十字迷宫和封闭场活动测试分析学习和记忆行为，同时评估的氧化应激参数为丙二醛（MDA）和谷胱甘肽。行为测试在第17、18和19天进行。与假手术大鼠相比，被动回避范式和高架十字迷宫中的缺陷表明大鼠在学习、记忆和认知行为方面出现了显著缺陷。在第21天，大鼠在乙醚麻醉下处死，对大脑进行生化研究分析。丙二醛（MDA）水平显著升高和谷胱甘肽水平降低表明大脑出现了氧化应激。该研究表明，脑室内注射STZ可能是研究抗氧化剂作为阿尔茨海默病痴呆潜在治疗方法的合适模型。
